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Medical errors resulting in patient harm still occur at an alarmingly high rate. Surgery is a high-risk area that can frequently result in patient harm if errors occur. There is a need for standardization of communication and processes to decrease errors. We sought to determine whether the implementation of a preoperative huddle at our hospital could standardize communication and decrease medical errors.A unique preoperative huddle was developed and implemented at a level 1 trauma center. We reviewed data before and after the implementation of the preoperative huddle including patient surveys and comments, the percentage of on-time operating room (OR) starts, OR turnover times, and the number of sentinel events.After huddle implementation, we observed a trend of improvement in our patient survey results on patient's perception that the doctors/nurses explained the procedure understandably after huddle implementation. There was a statistically yet limited clinically significant increase in OR turnover time from 37 to 40 minutes (P0.001). There was also an increase in on-time OR starts from 37% to 45% (P0.001). We observed a decrease in the number of sentinel events, with only 1 occurring each year since implementation.A preoperative huddle was successfully implemented at a level 1 trauma hospital and helped standardize communication without significantly disrupting workflow. To our knowledge, this method of preoperative huddling has not been previously described in the literature.

Critically ill patients infected with SARS-CoV-2 display adaptive immunity, but it is unknown if they develop cross-reactivity to variants of concern (VOCs). We profiled cross-immunity against SARS-CoV-2 VOCs in naturally infected, non-vaccinated, critically ill COVID-19 patients. Wave-1 patients (wild-type infection) were similar in demographics to Wave-3 patients (wild-type/alpha infection), but Wave-3 patients had higher illness severity. Wave-1 patients developed increasing neutralizing antibodies to all variants, as did patients during Wave-3. Wave-3 patients, when compared to Wave-1, developed more robust antibody responses, particularly for wild-type, alpha, beta and delta variants. Within Wave-3, neutralizing antibodies were significantly less to beta and gamma VOCs, as compared to wild-type, alpha and delta. Patients previously diagnosed with cancer or chronic obstructive pulmonary disease had significantly fewer neutralizing antibodies. Naturally infected ICU patients developed adaptive responses to all VOCs, with greater responses in those patients more likely to be infected with the alpha variant, versus wild-type.

Planning plays a key role in ensuring the provision of adequate residential land exists for housing development. This paper explores the failure of housing land supply policy in Wales from multiple policy failure perspectives, ultimately identifying three key findings. Firstly, the goal-orientated failure in achieving five-year housing land supply is evident. Secondly, the reasons for failure vary but focus on the ramifications of the calculations and also relationships of planners and housebuilders across the public and private sector. Finally, despite the explanations cited for failure, the need for five-year land supply calculations to facilitate housing provision remains an unquestioned necessity.

Discussion is a crucial component for learning in a college classroom. Increasingly, university and college faculty are using online learning management systems to facilitate and assess course disc...

De novo gene synthesis is the state-of-the-art method used to obtain genetic material adapted to the requirements of the host organism and a cornerstone for modern synthetic biology. Yet, little progress has been made regarding downstream processes of protein production from synthetic genetic material. The production of recombinant proteins traditionally requires extensive preparatory work including gene amplification, cloning, sequencing, transformation or transfection of the expression host, cultivation of living cells, and purification of the overexpressed protein. In this work we describe a fast and automated workflow for cell-free production of proteins starting from an electronic protein sequence or accession number. PRESTO (protein expression starting from oligonucleotides) seamlessly combines a tailored in silico sequence optimization with the assembly of short oligonucleotides into synthetic linear DNA expression cassettes, mammalian in vitro transcription/translation, and protein purification thereof. Integrated on a small liquid handling system it provides a hands-free high throughput source for functional synthetic proteins within 1 day.

Toronto’s Quayside waterfront regeneration project has become an international reference point for the burgeoning debate about the scope and limits of the digitally enabled ‘smart city’ narrative. The project signals the entry of a Google affiliate into the realm of ‘smart urbanism’ in the most dramatic fashion imaginable, by allowing them to potentially realise their long-running dream for “someone to give us a city and put us in charge.” This article aims to understand this on-going ‘smart city’ experiment through an exploration of the ways in which ‘techno-centric’ narratives and proposed ‘disruptive’ urban innovations are being contested by the city’s civic society. To do this, the article traces the origins and evolution of the partnership between Waterfront Toronto and Sidewalk Labs and identifies the key issues that have exercised local critics of the plan, including the public/private balance of power, governance, and the planning process. Despite more citizen-centric efforts, there remains a need for appropriate advocates to protect and promote the wider public interest to moderate the tensions that exist between techno-centric and citizen-centric dimensions of smart cities.

This editorial introduces the thematic issue on “Vertical Cities: The Development of High-Rise Neighbourhoods.” It outlines the lack of understanding about high-rise development in cities around the world and argues for a continued need to further interrogate concepts of verticality beyond single towers and towards a finer grain examination of high-rise neighbourhoods. The editorial introduces four interconnected themes that begin to address this phenomenon—socio-demographic challenges, planning discourses, high-rise legacies, and alternative conceptions of verticality—and highlights how the various articles in this thematic issue explore these critical areas of enquiry. It concludes with a call for future research to delve deeper into the planning challenges presented by high-rise neighbourhoods in the 21st-century city and, critically, the contribution that high-rise urban form makes to urban sustainability.

While fluorescence readout is a key detection modality for hydrogel-based immunoassays, background fluorescence due to autofluorescence or non-specific antibody interactions impairs the lower limit of detection of fluorescence immunoassays. Chemical modifications to the hydrogel structure impact autofluorescence and non-specific interactions. Benzophenone is a common photoactivatable molecule, and benzophenone methacrylamide (BPMA) has been used for cross-linking protein in polyacrylamide (PA) hydrogels. However, previous studies have suggested that the aromatic structure of benzophenone can contribute to increased autofluorescence and non-specific hydrophobic interactions with unbound fluorescent probes. Here, we synthesize diazirine methacrylamide (DZMA) as an alternative photoactivatable molecule to crosslink into PA hydrogels for in-gel protein capture for in-gel immunoassays. We hypothesize that the less hydrophobic structure of diazirine (based on previously reported predicted and experimental log P values) exhibits both reduced autofluorescence and non-specific hydrophobic interactions. We find that while equal concentrations of DZMA and BPMA result in lower protein target photocapture in the diazirine configuration, increasing the DZMA concentration up to 12 mM improves in-gel protein capture to be on par with previously reported and characterized 3 mM BPMA hydrogels. Furthermore, despite the higher concentration of diazirine, we observe negligible autofluorescence signal and a 50% reduction in immunoassay fluorescence background signal in diazirine gels compared to BPMA gels resulting in comparable signal-to-noise ratios (SNR) of the probed protein target. Finally, we test the utility of DZMA for single-cell immunoblotting in an open microfluidic device and find that protein migrates ∼1.3× faster in DZMA hydrogels than in BPMA hydrogels. However, in DZMA hydrogels we detect only 15% of the protein signal compared to BPMA hydrogels suggesting that the diazirine chemistry results in greater protein losses following electrophoretic separations. We establish that while diazirine has lower background fluorescence signal, which may potentially improve immunoassay performance, the lower capture efficiency of diazirine reduces its utility in open microfluidic systems susceptible to sample losses.

Do lobby groups help the American president achieve policy objectives? Existing research seldom evaluates interest groups and the president in conjunction, and as a result we have little systematic...

Household projections have been a critical tool in establishing top-down hierarchical frameworks through which planning systems impose new housing requirements on localities. This paper re-assesses the role of household projections in the context of two recent factors. The first is the emergence of increasingly localised spatial governance arrangements that enhance the scope to challenge household projections data. The second is the gradual emergence of the economy from recession and its impact on interpretation of household projections data. A case study of planning for housing in Wales explores the ambiguities and conflicts that arise as a result of these changes.

This chapter discusses the potential use of GIS in social policy analysis. It describes the advantages of GIS as an approach to social policy enquiry and provides a number of extant examples from a variety of policy fields. Although it is typically thought of as a quantitative method, the chapter also emphasises more recent qualitative uses of GIS. The chapter addresses some of the barriers to the use of GIS in social policy and how these can be overcome. The chapter concludes with an overview of how recent innovations in GIS and the availability of social data can have a positive impact on the use of GIS in the field of social policy.

Luciferase-based reporter assays are powerful tools for monitoring gene expression in cells because of their ultrasensitive detection capacity and wide dynamic range. Here we describe the characterization and use of a luciferase reporter enzyme derived from the marine copepod Metridia luciferase family, referred to as TurboLuc luciferase (TurboLuc). To develop TurboLuc, the wild-type luciferase was modified to decrease its size, increase brightness, slow luminescent signal decay, and provide for efficient intracellular expression. To determine the enzyme susceptibility to compound inhibition and judge the suitability of using of TurboLuc as a reporter in screening assays, purified TurboLuc enzyme was screened for inhibitors using two different compound libraries. No inhibitors of this enzyme were identified in a library representative of typical diverse low molecular weight (LMW) compounds using a purified TurboLuc enzyme assay supporting that such libraries will show very low interference with this enzyme. We were able to identify a few inhibitors from a purified natural product library which can serve as useful tools to validate assays using TurboLuc. In addition to the inhibitor profile for TurboLuc we describe the use of this reporter in cells employing miniaturized assay volumes within 1536-well plates. TurboLuc luciferase is the smallest luciferase reporter enzyme described to date (16 kDa), shows bright luminescence and low interference by LMW compounds, and therefore should provide an ideal reporter in assays applied to high-throughput screening.

An interview transcript can be a rich source of geographical references whose potential are not always fully realised in their conventional analysis. Geo‐referencing techniques can be used to assign a spatial footprint to place names, adding value to these data and allowing the geographic information within them to be exploited when coupled with GIS technology. This paper discusses a method of analysing and visualising interview transcripts in order to understand the spatial extent of public policy practitioners’ activities. Through aggregation and statistical mapping it is possible to gain insight into the importance of space across a range of public policy themes and to understand the relationship between practitioner‐defined policy themes and the formal administrative boundaries within which they typically work. The research demonstrates that spatial working practices rarely conform to formal administrative boundaries and that there are varying degrees of spatial focus between different policy themes within localities. It also reveals that spatial working practices can continue to be influenced by historic geographies and can be pulled in different directions, reflecting both the devolved nature of the sector and the particular geographical context of the setting. It concludes that mapping the interview transcript can add value and provide additional insights to more conventional analysis.

The publication of the UK Government's 'National Infrastructure Plan' by the Treasury in 2010 (HM Treasury and UK Infrastructure) acknowledged the need for major infrastructure investment, both new and replacement, to achieve sustainable and balanced economic and environmental development. More importantly, it marked a commitment from the government and other key stakeholders to develop a more strategic approach towards infrastructure planning. These policies and the wider shifts in infrastructure - both physical and electronic - will have massive impacts across the UK, not least on the functional economies of different regions.In the northern regions of England (the North West, North East and Yorkshire and Humber), which have traditionally been seen as economically lagging, historical and current policies have impacted upon their ability to attract infrastructure investment. Yet within these northern regions, infrastructure funding, development and accessi- bility are spatially diverse. Two distributional drivers are of particular concern. First, is the ability of the north to compete with other more economically buoyant regions for infrastructure investment; second, is the equitable spatial distribution of that investment throughout the north's towns and cities. It is this need to balance competi- tive market demand for investment with wider strategic and equitable distributional policy concerns that makes the lagging northern regions interesting research subjects throughout which to examine a range of contemporary issues concerning infrastruc- ture delivery and the way it can create new transitional pathways of development. The north of England is therefore used in this special edition of Town Planning Review as a case study to explore the ways in which infrastructure might influence different transitional pathways. In doing so, it discusses in some depth a range of issues related to understanding the scale of the infrastructure challenge and how this impacts on space and people; how best to determine the cost and benefits of infrastructure devel- opment and how that influences decisions; the most appropriate methods by which infrastructure should be planned to develop those pathways; and the future potential that appropriately planned infrastructure can have for lagging regions.A scoping conference on 'Enabling a strategic approach to transformational infrastructure' sponsored by the N8 Universities Partnership was held at Manchester Business School in February 2012, with twenty-five leading researchers, infrastructure providers, industries, management consultants and policymakers. The future research agenda identified by the stakeholders is discussed in more detail by Cecilia Wong and Brian Webb in this issue, but broadly points to the need to map out the transfor- mational pathways of spatial development by better understanding how infrastruc- ture can be delivered in different ways to positively and progressively transform the economic, environmental and social outlook under different spatial contexts. This special issue of Town Planning Review thus seeks to build on the earlier N8 conference discussions and explore key ideas and concepts related to the dynamic interaction between planning policy and practice and infrastructure development and imple- mentation. In doing so, it places particular emphasis on planning for infrastructure in the three northern regions of England, where economic growth is viewed as stagnant in comparison to other regions. The challenges that lagging regions, such as those in the north of England, present when planning for infrastructure, as well as the poten- tial impact infrastructure could have on improving economic and social planning outcomes in these places, are addressed in the five papers that follow this introduction.The north-south divide is a well-established concept in the UK literature, yet there is a lack of debate about how infrastructure provision may be used to either perpet- uate this socio-economic divide or help to bridge it. …

Long-neglected, infrastructure planning has returned to the political limelight in the UK. While the debate has been preoccupied with the financial, efficiency and regulatory aspects of major infrastructure development, there is a lack of systematic understanding of the spatial issues. This paper seeks to provide an overview of the changing policy environment of infrastructure planning in regards to spatial distribution patterns in England. It also explores the knowledge gaps, policy questions and challenges of infrastructure development in the lagging northern regions. It concludes with a discussion aimed at shaping a future research agenda and actions for infrastructure planning in lagging regions.

This chapter discusses the need to consider the relations between the material, social, and cultural dimensions of well-being in a rural environment through an exploration of low income people and the ways in which they view and contextualise their lives. To do this, it draws on survey and interview material from a study of poverty in rural Wales, United Kingdom, highlighting the ways in which people on low income understand their quality of life more in relation to their social and cultural worlds than to material deprivation and relative lack of income. The research reveals that quality of life is often discussed through community belonging and attachment to landscape, which are more valued in rural poor people’s narratives, compared to material hardship and social exclusion which are less pronounced as a factor impacting their quality of life. The chapter concludes by exploring the potential impacts of such perspectives in relation to recent governmental policy changes.

The loss of dopaminergic neurons induced by the parkinsonian toxins paraquat, rotenone, and 1-methyl-4-phenylpyridinium (MPP + ) is associated with oxidative stress. However, controversial reports exist regarding the source/compartmentalization of reactive oxygen species (ROS) generation and its exact role in cell death. We aimed to determine in detail the role of superoxide anion (O 2 •- ), oxidative stress, and their subcellular compartmentalization in dopaminergic cell death induced by parkinsonian toxins. Oxidative stress and ROS formation were determined in the cytosol, intermembrane (IMS), and mitochondrial matrix compartments, using dihydroethidine derivatives and the redox sensor roGFP, as well as electron paramagnetic resonance spectroscopy. Paraquat induced an increase in ROS and oxidative stress in both the cytosol and the mitochondrial matrix prior to cell death. MPP + and rotenone primarily induced an increase in ROS and oxidative stress in the mitochondrial matrix. No oxidative stress was detected at the level of the IMS. In contrast to previous studies, overexpression of manganese superoxide dismutase (MnSOD) or copper/zinc SOD (CuZnSOD) had no effect on alterations in ROS steady-state levels, lipid peroxidation, loss of mitochondrial membrane potential (ΔΨm), and dopaminergic cell death induced by MPP + or rotenone. In contrast, paraquat-induced oxidative stress and cell death were selectively reduced by MnSOD overexpression, but not by CuZnSOD or manganese-porphyrins. However, MnSOD also failed to prevent ΔΨm loss. Finally, paraquat, but not MPP + or rotenone, induced the transcriptional activation of the redox-sensitive antioxidant response elements (ARE) and nuclear factor kappa-B (NF-κB). These results demonstrate a selective role of mitochondrial O 2 •- in dopaminergic cell death induced by paraquat, and show that toxicity induced by the complex I inhibitors rotenone and MPP + does not depend directly on mitochondrial O 2 •- formation.

Purpose In vitro transcription/translation (IVTT) systems are widely used in proteomics. For clinical applications, mammalian systems are preferred for protein folding and activity; however, the level of protein obtained is low. A new system extracted from human cells (1-Step Human Coupled IVT (HCIVT)) has the potential to overcome this problem and deliver high yields of protein expressed in a human milieu. Experimental design Western blots and self-assembled protein microarrays were used to test the efficiency of protein synthesis by HCIVT compared to rabbit reticulocyte lysate (RRL). The arrays were also used to measure the immune response obtained from serum of patients exposed to pathogens or vaccine. Results HCIVT performed better than RRL in all experiments. The yield of protein synthesized in HCIVT is more than ten times higher than RRL, in both Western blot and protein microarrays. Moreover, HCIVT showed a robust lot-to-lot reproducibility. In immune assays, the signals of many antigens were detected only in HCIVT-expressed arrays, mainly due to the reduction in the background signal and the increased levels of protein on the array. Conclusion and clinical relevance HCIVT is a robust in vitro transcription and translation system that yields high levels of protein produced in a human milieu. It can be used in applications where protein expression in a mammalian system and high yields are needed. The increased immunogenic response of HCIVT-expressed proteins will be critical for biomarker discovery in many diseases, including cancer.

According to currently available estimates from Cancer Research UK, 14.1 million new lung cancer cases were diagnosed and a staggering 8.2 million people worldwide died from lung cancer in 2012. EGFR and c-Met are two tyrosine kinase receptors most commonly overexpressed or mutated in Non-small Cell Lung Cancer (NSCLC) resulting in increased proliferation and survival of lung cancer cells. Tyrosine kinase inhibitors (TKIs), such as erlotinib, approved by the FDA as first/second line therapy for NSCLC patients have limited clinical efficacy due to acquired resistance. In this manuscript, we investigate and discuss the role of epithelial mesenchymal transition (EMT) in the development of resistance against EGFR and c-Met TKIs in NSCLC. Our findings show that Zeb-1, a transcriptional repressor of E-Cadherin, is upregulated in TKI-resistant cells causing EMT. We observed that TKI-resistant cells have increased gene and protein expression of EMT related proteins such as Vimentin, N-Cadherin, β-Catenin and Zeb-1, while expression of E-Cadherin, an important cell adhesion molecule, was suppressed. We also confirmed that TKI-resistant cells display mesenchymal cell type morphology, and have upregulation of β-Catenin which may regulate expression of Zeb-1, a transcriptional repressor of E-Cadherin in TKI-resistant NSCLC cells. Finally, we show that down-regulating Zeb-1 by inducing miR-200a or β-Catenin siRNA can increase drug sensitivity of TKI-resistant cells.

This paper discusses the extent to which the science of urban climatology has informed local climate change strategies in four city case studies – Stuttgart, Tokyo, New York City, and Manchester. The paper draws on historical and contemporary policy documents along with sixty interviews with practitioners, city officials, politicians and academics in order to understand the use or non-use of urban climatology science in local climate change strategies. It explores the historic successes and failures of urban climate management of the cities and how the impact of global climate change and perception of risk, local competency and capacity, national programmes, and the involvement of cities in networks influences the application, stabilization and institutionalization of urban climatology into climate change strategies. It concludes by highlighting the high levels of variability present and potential reasons for local policy engagement or non-engagement in the use of urban climatology science.

It has long been acknowledged that there is a gap between the advancement of GIS in the research field and its application in planning practice. This paper demonstrates the potential for employing simple GIS mapping overlays as a way of communicating complex planning issues in a ‘language’ that is easily understandable and effective at stimulating policy debate, critical thinking, and learning. The analysis focuses on capturing the synergies and conflicts in two key planning challenges in England, progrowth and housing delivery agendas. In a political context where spatial evidence-based policy making has been eroded in recent years, the analysis demonstrates the need for policy makers to ‘think spatially, act spatially’ when developing different policies and programmes. The paper concludes that only by making spatial relationships of policies and programmes explicit in a manner that is easily understood by a range of actors, can different spatial scenarios and metaphors of future opportunities and challenges be developed to inform long-range development and planning.